crossing96/oncoscreening huggingface dataset:
Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer?	The aim of our study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR) is a predictor of disease progression and recurrence in patients with primary non-muscle-invasive bladder cancer (NMIBC). This was a prospective study of 86 patients with newly diagnosed NMIBC. The patients were classified by the number of points assigned by the European Organization for Research and Treatment of Cancer risk tables. The correlation between progression score, recurrence score, age, mean platelet volume, red blood cell distribution width and NLR was assessed statistically. The same parameters were compared between the risk groups. A significant difference in NLR and age values was observed between recurrence and progression risk score groups. The relationships between NLR and recurrence and progression risk scores were no longer significant after correcting for the statistical effect of age on scores. Age was significantly different between groups after adjusting for NLR. Our study revealed that NLR and age were associated with patient age and bladder tumor progression and recurrence risk scores. After correcting for age, the significant relationship with NLR was lost, in contrast to some previous studies. We recommend that patient age should be corrected to avoid misleading results in NLR studies.	bladder
Lymphoepithelioma-like carcinoma of the bladder: A case report.	type of low differentiated carcinoma of the nasopharyngeal region characterized by marked infiltration of lymphocytes in the area involved by tumor. However, carcinomas with this peculiar morphologic feature have been also described in various anatomic locations and they are generally designated «lymphoepithelioma-like carcinomas». Those of the urinary bladder are uncommon as they account of 0.4%-1.3% of all bladder carcinomas. They may coexist with the conventional urothelial carcinoma. Given their rarity, there is poor information regarding their behaviour. Here we present a new case of lymphoepithelioma-like carcinoma in the bladder and we discuss its characteristics and prognosis.	bladder
Essential content of evidence-based clinical practice guidelines for bladder cancer: The Japanese Urological Association 2015 update.	The Japanese Urological Association revised the clinical practice guidelines for bladder cancer in April 2015. This was the first update carried out in the 6 years since the development of the initial clinical practice guidelines for bladder cancer in 2009. The descriptive content was revised, and additions were made with a focus on new-found evidence and advances in the latest medical practices, and on the basis of the increasingly aging population observed in the underlying social context in Japan. An algorithm for the treatment of bladder cancer has been presented as a new trial. In the present article, we will introduce the essential contents and clinical questions that address the present revisions.	bladder
[A case of Mullerian duct cyst torsion combined with bladder cancer].	The diagnosis and treatment of a patient with Mullerian duct cyst torsion combined with bladder cancer were retrospectively analyzed. The patient received an open abdominal operation with right accessory resection plus pelvic adhesion release, and conducted microscopic examination for the bladder under general anesthesia. The results of histopathological examination confirmed the diagnosis of Mullerian duct cyst and papillary urothelial carcinoma at low level. After surgery, the patient received chemotherapy and follow-up observation, and all the indices for the patient were normal and no obvious discomfort. Although the final diagnosis of Mullerian duct cysts is based on histopathological examination, ultrasonography, CT scan and MRI can also detect it. Most of the Mullerian duct cysts are benign, and surgical excision is safe and effective.	bladder
Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment.	Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) and monocarboxylate transporter 1 (MCT1) play important roles in tumor endothelial cells (ECs) and several biological processes. The present study was conducted to study the effects of PFKFB3 and MCT1 on cell proliferation and apoptosis in the tumor microenvironment by co-culture of HUVECs and T24, a bladder cancer (BC) cell line, using a microfluidic device. Immunofluorescence assay showed that HUVEC activity was significantly enhanced under co-culture with T24 cells, according to the stronger fluorescence intensity of CD31 and CD105 than that in the signal‑cultured cells. Quercetin treatment inhibited MCT1 expression but did not affect PFKFB3 expression. Knockdown of MCT1 or/and PFKFB3 increased the apoptosis rate of the HUVECs under single-culture and co-culture situations by staining with calcein and propidium iodide. Meanwhile, cell proliferation and lactic concentration were significantly decreased after the blocking of MCT1 or/and PFKFB3, as compared with that in the control group. No obvious differences in the effects on apoptosis, proliferation and lactic concentration were found between cells treated with quercetin and siMCT1. Thus, we concluded that the targeting of MCT1 and PFKFB3 regulated cell proliferation and apoptosis in BC cells by altering the tumor microenvironment, and quercetin exhibited a potential antitumor effect by targeting MCT1.	bladder
Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1).	Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.	bladder
Low Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts for Good Outcomes in Patients Receiving Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle Invasive Bladder Cancer.	PURPOSE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been associated with cancer prognosis, influencing progression and chemosensitivity. We aimed to define the role of the NLR in predicting the outcomes to neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: The data from patients treated with NAC and radical cystectomy for MIBC from 2007 to 2015 at a tertiary care center were reviewed. The clinicopathologic pretreatment, including the NLR, and post-treatment predictors were documented. The NLR was evaluated as a continuous variable on uni- and multivariate analysis and dichotomized in Kaplan-Meier curves. The relationships with outcomes (progression-free survival [PFS], cancer-specific survival [CSS], and overall survival [OS]) were analyzed using Cox regression analysis and log-rank tests. The pathologic response (PR) included any downstaging from the baseline clinical stage to the final pathologic stage. RESULTS: Of 205 patients with MIBC, 75 underwent NAC (median follow-up, 31 months) with a 5-year PFS, CSS, and OS rate of 56%, 60%, and 52%, respectively, and a PR of 38.6%. On multivariate analysis, the PR, PFS, CSS, and OS were predicted by the NLR (hazard ratio > 0.8, 1.25, 1.27, and 1.12, respectively; P < .05 for all). The NLR with age and clinical stage predicted the PR. A NLR threshold of 2.26 better predicted CSS (P < .05) and OS (P = .055). The limitations included the retrospective design and modest number of cases. CONCLUSION: We have provided initial evidence that a low NLR helps understand the value of the underlying immune system in predicting a good outcome to NAC. The NLR is a simple and accessible biomarker that is easy to implement in clinical practice. In addition to established prognosticators and newer genomic predictors, the NLR could improve therapeutic algorithms and help in decision-making regarding the need for NAC, which is currently underused, in MIBC patients.	bladder
BLCA-4 and UBC combined detection for early diagnosis of bladder cancer.	The objective of the present study was to report the clinical significance of bladder cancer specific nuclear matrix protein 4 (BLCA-4) and urinary bladder cancer (UBC) on early diagnosis of bladder cancers. Enzyme-linked immunosorbent assay (ELISA) was used to detect BLCA-4 and UBC of 56 bladder cancer patients and 26 patients with urinary tract benign diseases, serving as controls. Urine exfoliated cell test was performed, and then the significance of BLCA-4 and UBC on the diagnosis of bladder cancers was analyzed. The sensitivity of BLCA-4 and UBC of the bladder cancer patients was significantly higher than that of the urine exfoliated cell test (P less than 0.05). The difference of BLCA-4 and UBC was not significant (P >0.05). The difference of BLCA-4 and UBC in the tumors with different gradings and stagings was not significant (P >0.05). Combined detection of BLCA-4 and UBC could improve the diagnosis sensitivity and specificity of bladder cancers with the advantages of high maneuverability, repeatability and objective results.	bladder
Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification.	The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.	bladder
Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy.	BACKGROUND: Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC). METHODS: RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who received cisplatin. A miR panel based on relevance for platinum sensitivity and UC was studied by quantitative reverse transcription quantitative PCR (RT-qPCR). Association of progression-free survival (PFS) with miR expression was analysed using cox regression. Selected TFs were chosen by association with the panel of miRs using the Transcription Regulation algorithm (GeneGo MetaCore+MetaDrug version 6.23 build 67496). Bladder cancer (BC) cell lines were used to investigate the previously described role of miR-21 mediating cisplatin sensitivity. RESULTS: The 83 patients had a median PFS of 8 months. In multivariate analysis, higher levels of E2F1 (P=0.01, HR: 1.95 (1.14, 3.33)), miR-21 (P=0.01, HR: 2.01 (1.17, 3.45)) and miR-372 (P=0.05, HR: 1.70 (1.00, 2.89)) were associated with a shorter PFS. In the 8 BC cell lines, miR-21 was not shown to be necessary nor sufficient for modulating cisplatin sensitivity. CONCLUSIONS: In metastatic UC patients treated with cisplatin-based therapy, high primary tumour levels of E2F1, miR-21 and miR-372 are associated with poor PFS independent of clinical prognostic factors. The in vitro study could not confirm miR-21 levels role in modulating platinum sensitivity.	bladder
First-Line Atezolizumab Effective in Bladder Cancer.	Results from a phase II study indicate that the PD-L1 inhibitor atezolizumab, recently approved for advanced bladder cancer that's refractory to standard platinum chemotherapy, is effective as first-line therapy for this disease. Durable responses to atezolizumab were seen in nearly a quarter of the study patients, who were all ineligible to receive cisplatin.	bladder
ALKBH8 promotes bladder cancer growth and progression through regulating the expression of survivin.	Human AlkB homolog 8 (ALKBH8) is highly expressed in high-grade, superficially and deeply invasive bladder cancer. Moreover, ALKBH8 knockdown induces apoptosis in bladder cancer cells. However, the underlying anti-apoptotic mechanism of ALKBH8 in bladder cancer cells has thus far remained unclear. Moreover, there is no direct evidence that highly expressed ALKBH8 is involved in tumor progression in vivo. We here show that ALKBH8 knockdown induced apoptosis via downregulating the protein expression of survivin, an anti-apoptotic factor also exhibiting increased levels in bladder cancer. We also clarify that ALKBH8 transgenic mice showed an accelerated rate of bladder tumor mass and invasiveness in an N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced bladder cancer model. These findings suggest that the high expression of ALKBH8 is critical for the growth and progression of bladder cancer.	bladder
Immune checkpoint blockade therapy for bladder cancer treatment.	Bladder cancer remains the most immunogenic and expensive malignant tumor in the United States today. As the 4th leading cause of death from cancer in United States, Immunotherapy blocking immune checkpoints have been recently been applied to many aggressive cancers and changed interventions of urological cancers including advanced bladder cancer. The applied inhibition of PD-1-PD-L1 interactions can restore antitumor T-cell activity and enhance the cellular immune attack on antigens. The overall goals of this short review article are to introduce current cancer immunotherapy and immune checkpoint inhibitors, and to provide new insight into the underlying mechanisms that block immune checkpoints in tumor microenvironment. Furthermore, this review will address the preclinical and clinical trials to determine whether bladder cancer patients could benefit from this new cancer therapy in near future.	bladder
The role of microRNAs in bladder cancer.	"Bladder cancer (BC) is the fifth most common cancer worldwide and is associated with significant morbidity and mortality. The prognosis of muscle invasive BC is poor, and recurrence is common after radical surgery or chemotherapy. Therefore, new diagnostic methods and treatment modalities are critical. MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs have important roles in the regulation of genes involved in cancer development, progression, and metastasis. The availability of genomewide miRNA expression profiles by deep sequencing technology has facilitated rapid and precise identification of aberrant miRNA expression in BC. Indeed, several miRNAs that are either upregulated or downregulated have been shown to have associations with significant cancer pathways. Furthermore, many miRNAs, including those that can be detected in urine and blood, have been studied as potential noninvasive tumor markers for diagnostic and prognostic purposes. Here, we searched PubMed for publications describing the role of miRNAs in BC by using the keywords ""bladder cancer"" and ""microRNA"" on March 1, 2016. We found 374 papers and selected articles written in English in which the level of scientific detail and reporting were sufficient and in which novel findings were demonstrated. In this review, we summarize these studies from the point of view of miRNA-related molecular networks (specific miRNAs and their targets) and miRNAs as tumor markers in BC. We also discuss future directions of miRNA studies in the context of therapeutic modalities."	bladder
Aberrantly expressed microRNAs in the context of bladder tumorigenesis.	MicroRNAs (miRNAs), small noncoding RNAs 19-22 nucleotides in length, play a major role in negative regulation of gene expression at the posttranscriptional level. Several miRNAs act as tumor suppressors or oncogenes that control cell differentiation, proliferation, apoptosis, or angiogenesis during tumorigenesis. To date, 19 research groups have published large-scale expression profiles that identified 261 miRNAs differentially expressed in bladder cancer, of which 76 were confirmed to have consistent expression patterns by two or more groups. These consistently expressed miRNAs participated in regulation of multiple biological processes and factors, including axon guidance, cancer-associated proteoglycans, and the ErbB and transforming growth factorbeta signaling pathways. Because miRNAs can be released from cancer cells into urine via secreted particles, we propose that miRNAs differentially expressed between tissue and urine could serve as predictors of bladder cancer, and could thus be exploited for noninvasive diagnosis.	bladder
Treatment of bladder cancer in the elderly.	As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes.	bladder
Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice.	Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction. Moreover, myostatin, activin A, and pro-inflammatory cytokine production, FoxO3 expression and activation, NF-κB activation, MuRF-1 and MAFbx/atrogin-1 expression, and proteasome activity in muscle were significantly decreased in the TGCF group compared with the TGC group. In addition, insulin-like growth factor 1 (IGF-1) expression and formation, and IGF-1-regulated mTOR/p70S6k/4EBP-1 protein synthesis signalling were elevated in the TGCF group compared with the TGC group. Taken together, these results suggest that LMWF is a potential agent for preventing cancer cachexia-associated muscle atrophy during chemotherapy. Furthermore, the beneficial effect of LMWF may be attributed to suppressing NF-κB-evoked inflammation, myostatin and activin A production, and subsequent muscle proteolysis, and enhancing IGF-1-dependent protein synthesis.	bladder
Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer.	Cisplatin (CDDP)-based combination chemotherapy remains the mainstream treatment for advanced bladder cancer. However, its efficacy is often limited due to the development of resistance for which underlying mechanisms are poorly understood. Meanwhile, emerging evidence has indicated the involvement of androgen-mediated androgen receptor (AR) signals in bladder cancer progression. In this study, we aimed to investigate whether AR signals have an impact on sensitivity to CDDP in bladder cancer cells. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous AR and AR-negative 647V/5637 cells stably expressing AR were significantly more resistant to CDDP treatment at its pharmacological concentrations, compared with UMUC3-AR-shRNA and 647V-vector/5637-vector control cells, respectively. A synthetic androgen R1881 significantly reduced CDDP sensitivity in UMUC3, 647V-AR, or 5637-AR cells, and the addition of an anti-androgen hydroxyflutamide inhibited the effect of R1881. In these AR-positive cells, R1881 treatment also induced the expression levels of NF-κB, which is known to involve CDDP resistance, and its phosphorylated form, as well as nuclear translocation of NF-κB. In CDDP-resistant bladder cancer sublines established following long-term culture with CDDP, the expression levels of AR as well as NF-κB and phospho-NF-κB were considerably elevated, compared with respective control sublines. In bladder cancer specimens, there was a strong trend to correlate between AR positivity and chemoresistance. These results suggest that AR activation correlates with CDDP resistance presumably via modulating NF-κB activity in bladder cancer cells. Targeting AR during chemotherapy may thus be a useful strategy to overcome CDDP resistance in patients with AR-positive bladder cancer.	bladder